DNA methylation, in the mammalian genome, is an epigenetic modification that involves the transfer of a methyl group on the C5 position of cytosine to derive 5-methylcytosine. The role of DNA methylation in the development of the nervous system and the progression of neurodegenerative diseases such as Alzheimer’s disease has been an interesting research area. Furthermore, mutations altering DNA methylation affect neurodevelopmental functions and may cause the progression of several neurodegenerative diseases. Epigenetic modifications in neurodegenerative diseases are widely studied in different populations to uncover the plausible mechanisms contributing to the development and progression of the disease and detect novel biomarkers for early prognosis and future pharmacotherapeutic targets. In this manuscript, we summarize the association of DNA methylation with the pathogenesis of the most common neurodegenerative diseases, such as, Alzheimer’s disease, Parkinson’s disease, Huntington diseases, and amyotrophic lateral sclerosis, and discuss the potential of DNA methylation as a potential biomarker and therapeutic tool for neurogenerative diseases.